BIOTIN SULFOXIDE

Abstract

The ease with which the sulfur atom of biotin is oxidized by various agents makes the properties of the oxidation products of practical biochemical importance.Biotin is converted to the sulfone under relatively mild conditions (1, 2).The biological properties of the sulfone have been studied in some detail (3) and differ markedly from those of biotin; in fact, the sulfone shows pronounced antibiotin activity toward several microorganisms which require biotin for growth (4).On the other hand, the chemical and biological properties of the sulfoxide have received little attention.This compound has been assumed to be an intermediate in the oxidation of biotin to the sulfone, but its preparation and properties have not been described heretofore.This paper describes the synthesis of biotin sulfoxide, the preparation of two diastereoisomeric forms, and the isolation of one of these forms from a milk residue concentrate.A separate paper describes some of the biological activities of the isomeric sulfoxides (5).Interest in biotin sulfoxide initially arose in this Laboratory during work on the isolation of biotin from esterified milk residue concentrates (6).Chromatography of some of the crude fractions on alumina yielded a crystalline substance which differed in melting point, crystalline form, and solubility from biotin methyl ester, but which showed the same growthpromoting activity as biotin methyl ester in the yeast assay.The analytical results indicated the empirical formula CnH1804N& which corresponds to that of biotin methyl ester with an additional oxygen atom.The supposition that the compound was the sulfoxide of biotin methyl ester was strengthened when we prepared the same substance from biotin methyl ester by oxidation with amounts of hydrogen peroxide insufficient to permit formation of the sulfone.The product, m.p. 17%180", was identical in physical and chemical properties with the substance isolated from milk and showed the same high yeast growth activity.Attention was then turned to the preparation of the free acid, the substance which might be produced by the oxidation of biotin in natural materials.Biotin was treated with hydrogen peroxide in acetic acid, under conditions which readily yield the sulfone (l), except that the amount of reagent was limited to that expected to be required to form a sulfoxide.